Abstract
Background: Cryptococcal meningitis (CM) is a major cause of AIDS-related mortality in Africa. Detection of serum cryptococcal antigen (CrAg) predicts development of CM in antiretroviral (ART) naïve HIV-infected patients with severe immune depression. Systematic pre-ART CrAg screening and pre-emptive oral fluconazole is thus recommended. We postulated that a semi-quantitative CrAg screening approach could offer clinically relevant advantages.Methods: ART-naïve asymptomatic adult outpatients with <100 CD4 cells/mm3 presenting to the Yaoundé Central Hospital, Cameroon were screened for CrAg using the IMMY lateral flow assay (LFA). CrAg positive patients were consented for lumbar puncture and those with proven CM were treated with combination antifungal therapy and those with no CM were offered long-term oral fluconazole. Simultaneous on-site evaluation of CrAg detection using the new LFA Biosynex® CryptoPS test was performed and both tests were subsequently compared to a reference commercialized CrAg enzyme immunoassay (EIA).Results: Prevalence of serum CrAg in 186 screened adults was 7.5% (95%CI: 4.5–12.4). In CrAg positive patients, CM prevalence was 45.5% (95%CI: 18.3–75.7). IMMY and Biosynex CryptoPS strongly agreed in serum, plasma, and cerebrospinal fluid (Kappa: 98.4, 99.5, 100%, respectively, p < 0.001), and disagreed in urine (29 isolated positive CrAg in urine with IMMY, none with Biosynex and none of whom had proven CM). Compared to EIA, serum specificities were 96.6 and 98.3%, respectively. With Biosynex CryptoPS, all CM patients were serum T2-band positive compared to nonewithout CM. Median EIA reciprocal titre was 160 (IQR: 13.5–718.8) and titres >160 strongly correlated with proven CM and Biosynex CryptoPS T2-band positivity. During the 1-year follow up period, there was no incident case of CM among screened patients and overall incidence of all-cause mortality was 31.5 per 100 person-years-at-risk (95%CI: 23.0–43.1).Conclusion: HIV-associated asymptomatic cryptococcosis is common in Cameroon, warranting integrated systematic screening and treatment. Biosynex CryptoPS holds promise, at point of care, for rapidly stratifying CrAg positive patients for optimal management including lumbar puncture and combination antifungal therapy when needed.Summary findings: Prevalence of CrAg and meningitis (CM) is high in Cameroon. Biosynex CryptoPS is comparable to IMMY LFA in CrAg screening. Its T2-band correlates with high antigen titres and CM, thus promising for identifying patients requiring effective induction therapy.Note: This study was presented in part at the 10th International Conference on Cryptococcus and Cryptococcosis (ICCC) in Iguazu in Brazil from 26 to 30th March 2017 and won a prize oral presentation.
Highlights
Cryptococcal meningitis (CM) is a major cause of morbidity and mortality among patients with advanced HIV infection especially in resource limited settings
The second strategy consisted of pre-antiretroviral therapy (ART) systematic screening for cryptococcal antigen (CrAg) in blood in profoundly immune depressed patients followed by preemptive administration of fluconazole to CrAg positive patients (Micol et al, 2007; Jarvis et al, 2012)
In Cameroon where 4.3% (Group Technique Central du Comite National de Lutte contre le VIH/SIDA, 2015) of adults are HIVinfected, we found in those presenting with
Summary
Cryptococcal meningitis (CM) is a major cause of morbidity and mortality among patients with advanced HIV infection especially in resource limited settings. In the African setting (Rajasingham et al, 2017), in the latter patients with detectable untreated blood cryptococcal antigen (CrAg), about 25% subsequently develop CM within the first year of ART compared to as few as no cases in CrAg negatives (Jarvis et al, 2009). In this setting, two strategies to reduce the incidence of CM have been suggested. With Biosynex CryptoPS, all CM patients were serum T2-band positive compared to none
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